16α-Methylated Adrenal Hormones. 17α-Hydroxylation by the Glyoxylate Process

Abstract

Reduction of a small sample of 17/3-hydroxyestrane-2one (Via) with sodium borohydride in ethanol water for 2 hr. afforded from benzene-petroleum ether hexagonal prisms, m.p. 208-210°, identical with the estrane 2a,17/3-diol (VIb) obtained above by mixed melting point and infrared spectra comparison.Estrane-176-ol (VIc). (a) By Huang-Minlon reduction of 176-hydroxyestrane-3-one (V). To a solution of 50 mg. of 17/3-hydroxyestrane-3-one (V) in 7 cc. of ethanol and 7 cc. of diethylene glycol 5 cc. of hydrazine hydrate was added.After refluxing for 30 min., 0.3 g. of solid potassium hydroxide was added and refluxing was continued for another 15 min. The condenser was then removed and the temperature of the solution was allowed to rise to 190°. Refluxing was then continued for 2.5 hr., at which point water was added and the mixture was extracted with ether. After washing with 5% hydrochloric acid, 5% sodium bicarbonate, and w'ater, the ether was dried and evaporated. The residue weighing 28 mg. was purified by sublimation at 90°, and subsequent crystallization from dilute ethanol. The estrane-17/3-ol (VIc) melted 130-133°( needles); [<*]d -8°.

Synthesis of Some Pregnane 16-Thioesters

“…at room temperature. 6 Only one isomer was readily isolated pure from a given reaction mixture. c In certain experiments the 16/3-isomer was isolated in 53-64% yields, isomer ratio ca.…”

“…1:1. d In one experiment a low yield of the 16a-isomer was obtained. 6 The isomer ratio, defined as the ratio of the 16/3-isomer content to the 16a-isomer content, was determined by nuclear magnetic resonance analysis of total reaction products, mother liquor fractions, etc., on the assumption that spurious lines in the C-18 methyl region (0.60-0.96 p.p.m.) not present in spectra of the pure isolated isomer were due to the presence of 16-isomeric products.…”